Results of high dose-rate brachytherapy boost before 2D or 3D external beam irradiation for prostate cancer

Background and purpose: To evaluate biochemical control and treatment related toxicity of patients with localized adenocarcinoma of the prostate treated with high dose-rate brachytherapy (HDRB) combined with conventional 2D or 3D-conformal external beam irradiation (EBI). Material and methods: Four-hundred and three patients treated between December 2000 and March 2004. HDRB was delivered with three fractions of 5.5-7 Gy with a single implant, followed by 45 Gy delivered with 2D or 3D conformal EBI. Results: The median follow-up was 48.4 months. Biochemical failure (BF) occurred in 9.6% according to both ASTRO and Phoenix consensus criteria. Mean time to relapse was 13 and 26 months, respectively. The 5-year BF free survival using the ASTRO criteria was 94.3%, 86.9% and 86.6% for the low, intermediate and high risk groups, respectively; using Phoenix criteria, 92.4%, 88.0% and 85.3%, respectively. The only predictive factor of BF in the multivariate analysis by both ASTRO and Phoenix criteria was the presence of prostate nodules detected by digital palpation, and patients younger than 60 years presented a higher chance of failure using Phoenix criteria only. Conclusions: Treatment scheme is feasible and safe with good efficacy. (C) 2011 Elsevier Ireland Ltd All rights reserved. Radiotherapy and Oncology 98 (2011) 169-174

The interaction between N-category and N-ratio as a new tool to improve lymph node metastasis staging in gastric cancer: Results of a single cancer center in Brazil

Background: Depth of tumor invasion (T-category) and the number of metastatic lymph nodes (N-category) are the most important prognostic factors in patients with gastric cancer. Recently, the ratio between metastatic and dissected lymph nodes (N-ratio) has been established as one. The aim of this study is to evaluate the impact of N-ratio and its interaction with N-category as a prognostic factor in gastric cancer. Methods: This was a retrospective study in which we reviewed clinical and pathological data of 165 patients who had undergone curative surgery at our institution through a 9-year period. The exclusion criteria included metastases, gastric stump tumors and gastrectomy with less than 15 lymph nodes dissected. Results: The median age of the patients was 63 years and most of them were male. Total gastrectomy was the most common procedure and 92.1% of the patients had a D2-lymphadenectomy. Their 5-year overall survival was 57.7%. T-category, N-category, extended gastrectomy, and N-ratio were prognostic factors in overall and disease-free survival in accordance with univariate analysis. In accordance with TNM staging, N1 patients who have had NR1 had 5-year survival in 75.5% whereas in the NR2 group only 33% of the cases had 5-year survival. In the multivariate analysis, the interaction between N-category and N-ratio was an independent prognostic factor. Conclusion: Our findings confirmed the role of N-ratio as prognostic factor of survival in patients with gastric cancer surgically treated with at least 15 lymph nodes dissected. The relationship between N-category and N-ratio is a better predictor than lymph node metastasis staging. (C) 2010 Elsevier Ltd. All rights reserved.

ERCC1 protein, mRNA expression and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma patients treated with surgery and adjuvant cisplatin-based chemoradiation

Adjuvant cisplatin-based chemoradiation improves survival in HNSCC patients presenting with risk features. ERCC1 (excision repair cross-complementation group 1) is associated with resistance to chemo- and radiation therapy and may have a prognostic value in HNSCC patients. Here we studied ERCC1 expression and the polymorphism T19007C as prognostic markers in these patients. This is a retrospective and translational analysis, where ERCC1 protein expression was evaluated by immunohistochemistry, using an H-score, and mRNA expression was determined by RT-PCR. T 19007C genotypes were detected by PCR-RFLP carried out using DNA template extracted from normal lymph nodes. A high H-score was seen in 32 patients (54%), who presented better 5-year overall survival (5-y OS: 50% vs. 18%, HR 0.43, p=0.026). Fifteen out of 45 patients (33%), with high mRNA expression, presented better 5-year overall survival (OS) (86% vs. 30%, HR 0.26, p=0.052). No OS difference was detected among T 19007C genotypes. High H-score and mRNA expression remained significant as favorable prognostic factors in a multivariate analysis. Collectively, our results suggest that high ERCC1 expression seems to be associated with better OS rates in HNSCC patients submitted to adjuvant cisplatin-based chemoradiation.

Expression Profile of p63 in 127 Patients with Laryngeal Squamous Cell Carcinoma

Objectives: To evaluate p63 expression in laryngeal squamous cell carcinoma and its prognostic significance. Methods: p63 expression was examined by immunohistochemistry and scored in 127 patients with laryngeal squamous cell carcinomas. Results: Sixty-two cases had scored 3, sixty had scored 2, four had scored 1 and one case did not show any expression (48.8, 47.2, 3.1 and 0.8%, respectively). Overall survival was 73.9% at 24 months and 59.5% at 60 months. The disease-free survival was 77.2 and 75.1%, and the disease-specific survival was 79 and 67% at 24 and 60 months, respectively. Uni- and multivariate analysis identified that decreased immunoexpression of protein p63 was a statistically significant factor for the risk of recurrence and death by cancer. Conclusions: p63 expression was highly prevalent in laryngeal squamous cell carcinomas, and its underexpression was correlated with a worse prognosis. Copyright (C) 2010 S. Karger AG, Basel

Voiding Dysfunction in Patients With Parkinson`s Disease: Impact of Neurological Impairment and Clinical Parameters

Aims: We assessed the lower urinary tract symptoms (LUTS) of patients with Parkinson`s disease (PD) and their association with different clinical parameters. Methods: We prospectively evaluated 110 patients (84 men), with a mean age of 61.8 +/- 9.6 years. Mean duration of the disease was 12.3 +/- 7.2 years. Neurological impairment was assessed by the Hoehn-Yahr and the Unified Parkinson Disease Rating scales. LUTS were assessed by the International Continence Society questionnaire. We evaluated the impact of age, PD duration, neurological impairment, gender, and use of anti-Parkinsonian drugs on the voiding function. Results: On multivariate analysis, voiding dysfunction increased with the neurological impairment, but not with patient`s age or disease duration. Quality of life (QOL) was affected by the severity of LUTS, and the symptoms with the worst impact were frequency and nocturia. Sixty-three (57.2%) patients were symptomatic. They did not differ with the asymptomatic as to age and disease duration, but had more severe neurological impairment. No impact on LUTS was associated with the use of levodopa, anticholinergics, and dopamine receptor agonists. Men and women were similarly affected by urinary symptoms. Conclusions: The severity of the neurological disease is the only predictive factor for the occurrence of voiding dysfunction, which affects men and women alike. Neztrourol. Urodynam. 28.510-515, 2009. (C) 2009 Wiley-Liss, Inc.

Pregnancy outcome in juvenile systemic lupus erythematosus: A Brazilian multicenter cohort study

Objective. To determine pregnancy outcome and fetal loss risk factors in patients with juvenile systemic lupus erythematosus (JSLE). Methods. A total of 315 female patients with JSLE followed in 12 Brazilian pediatric rheumatology centers were consecutively selected. Menarche was observed in 298 (94.6%) patients. Patients` medical records were reviewed for pregnancy outcomes and demographic, clinical, and therapeutic data. Results. A total of 24 unplanned pregnancies occurred in 298 (8%) patients. The outcomes were 5 (21%) early fetal losses (prior to 16 wks gestation), 18 (75%) live births, and 1 (4%) death due to preeclampsia and premature birth. The frequencies of active diffuse proliferative glomerulonephritis, proteinuria >= 0.5 g/day, and arterial hypertension at the beginning of pregnancy were higher in pregnancies resulting in fetal losses than in live births [60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), respectively]. JSLE pregnancies with fetal losses had a significantly higher mean SLE Disease Activity Index 2000 (SLEDAI-2K) at the start of pregnancy compared with those with live births (9.40 +/- 7.47 vs 3.94 +/- 6.00; p = 0.049). Four pregnancies were inadvertently exposed to intravenous cyclophosphamide therapy for renal involvement despite contraceptive prescriptions, resulting in fetal loss in 3 (p = 0.02). In multivariate analysis only intravenous cyclophosphamide use at start of pregnancy (OR 25.50, 95% CI 1.72-377.93, p = 0.019) remained as an independent risk factor for fetal loss. Conclusion. We identified immunosuppressive therapy as the major contributing factor for fetal loss in JSLE, reinforcing the importance of contraception.

Outpatient treatment with intravenous antimicrobial therapy and oral levofloxacin in patients with febrile neutropenia and hematological malignancies

The purpose of this study was to evaluate outcomes such as success of the initial therapy, failure of outpatient treatment, and death in outpatient treatment during intravenous antimicrobial therapy in patients with febrile neutropenia (FN) and hematological malignancies. In addition, clinical and laboratory data and the Multinational Association for Supportive Care of Cancer index (MASCC) were compared with failure of outpatient treatment and death. In a retrospective study, we evaluated FN following chemotherapy events that were treated initially with cefepime, with or without teicoplanin and replaced by levofloxacin after 48 h of defervescence in patients with good general conditions and ANC > 500/mm(3). Of the 178 FN episodes occurred in 126 patients, we observed success of the initial therapy in 63.5% of the events, failure of outpatient treatment in 20.8%, and death in 6.2%. The success rate of oral levofloxacin after defervescence was 99% (95 out of 96). Using multivariate analysis, significant risks of failure of outpatient treatment were found to be smoking (odds ratio (OR) 3.14, confidence interval (CI) 1.14-8.66; p = 0.027) and serum creatinine levels > 1.2 mg/dL (OR 7.97, CI 2.19-28.95; p = 0.002). With regard to death, the risk found was oxygen saturation by pulse oximetry < 95% (OR 5.8, IC 1.50-22.56; p = 0.011). Using the MASCC index, 165 events were classified as low risk and 13 as high risk. Failure of outpatient treatment was reported in seven (53.8%) high-risk and 30 (18.2%) low-risk episodes (p = 0.006). In addition, death occurred in seven (4.2%) low-risk and four (30.8%) high-risk events (p = 0.004). Ours results show that MASCC index was able to identify patients with high risk. In addition, non-smoking, serum creatinine levels a parts per thousand currency sign1.2 mg/dL, and oxygen saturation by pulse oximetry a parts per thousand yen95% were protection factors.

A prognostic score for AIDS-related diffuse large B-cell lymphoma in Brazil

The aim of this study was to evaluate a prognostic score for aids-related lymphoma (ARL). A retrospective study of 104 patients with ARL treated between January 1999 and December 2007 was conducted. Diffuse large B-cell lymphoma (DLBC) was the most observed histological type (79.8%). The median CD4 lymphocyte count at lymphoma diagnosis was 125 cells per microliter. Treatment response could be evaluated in 83 (79.8%) patients, and 38 (45.8%) reached complete remission (CR); overall response rate was 51.8% (95 CI = 38.5-65.1%). After a median follow-up of 48 months, the 4-year overall survival (OS) rate among all patients was 35.8%, with a median survival time of 9.7 months (95% CI = 5.5-13.9 months). The survival risk factors observed in multivariate analysis (previous AIDS and high-intermediate/high international prognostic index (IPI)) were combined to construct a risk score, which divided the whole patient population in three distinct groups as low, intermediate, and high risk. When this score was applied to DLBC patients, a clear distinction in response rates and in OS could be demonstrated. Median disease-free survival (DFS) for patients that achieved CR was not reached, and DFS in 4 years was 83.0%. Our results show that the reduced OS observed could be explained by poor immune status with advanced stage of disease seen in our population of HIV-positive patients. Further studies will be needed to clarify the role of different treatment approaches for ARL in the setting of marked immunosuppression and to identify a group of patients to whom intensive therapy could be performed with a curative intent.

Unexplained sudden death in patients on the waiting list for renal transplantation

Background. The incidence of unexplained sudden death (SD) and the factors involved in its occurrence in patients with chronic kidney disease are not well known. Methods. We investigated the incidence and the role of co-morbidities in unexplained SD in 1139 haemodialysis patients on the renal transplant waiting list. Results. Forty-four patients died from SD of undetermined causes (20% of all deaths; 3.9 deaths/1000 patients per year), while 178 died from other causes and 917 survived. SD patients were older and likely to have diabetes, hypertension, past/present cardiovascular disease, higher left ventricular mass index, and lower ejection fraction. Multivariate analysis showed that cardiovascular disease of any type was the only independent predictor of SD (P = 0.0001, HR = 2.13, 95% CI 1.46-3.22). Alterations closely associated with ischaemic heart disease like angina, previous myocardial infarction and altered myocardial scan were not independent predictors of SD. The incidence of unexplained SD in these haemodialysis patients is high and probably a consequence of pre-existing cardiovascular disease. Conclusions. Factors influencing SD in dialysis patients are not substantially different from factors in the general population. The role played by ischaemic heart disease in this context needs further evaluation.

Impact of number of vessels disease on outcome of patients with stable coronary artery disease: 5-year follow-up of the medical, angioplasty, and bypass surgery study (MASS)

Objective: To evaluate whether the number of vessels disease has an impact on clinical outcomes as well as on therapeutic results accordingly to medical, percutaneous, or surgery treatment in chronic coronary artery disease. Methods: We evaluated 825 individuals enrolled in MASS study, a randomized study to compare treatment options for single or multivessel coronary artery disease with preserved left ventricular function, prospectively followed during 5 years. The incidence of overall mortality and the composite end-point of death, myocardial infarction, and refractory angina were compared in three groups: single vessel disease (SVD n = 214), two-vessel disease (2VD n = 253) and three-vessel disease (3VD n = 358). The relationship between baseline variables and the composite end-point was assessed using a Cox proportional hazards survival model. Results: Most baseline characteristics were similar among groups, except age (younger in SVD and older in 3VD, p < 0.001), lower incidence of hypertension in SVD (p < 0.0001), and lower levels of total and LDL-cholesterol in 3VD (p = 0.004 and p = 0.005, respectively). There were no statistical differences in composite end-point in 5 years among groups independent of the kind of treatment; however, there was a higher mortality rate in 3VD (p < 0.001). When we stratified our analysis for each treatment option, bypass surgery was associated with a tower number of composite end-point in all groups (SVD p < 0.001, 2VD p = 0.002, 3VD p < 0.001). In multivariate analysis, we found higher mortality risk in 3VD comparing to SVD (p = 0.005, HR 3.14, 95%Cl 1.4-7.0). Conclusion: Three-vessel disease was associated with worse prognosis compared to single-or two-vessel disease in patients with stable coronary disease and preserved ventricular function at 5-year follow-up. In addition, event-free survival rates were higher after bypass surgery, independent of the number of vessels diseased in these subsets of patients. (c) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Depression: a predictor of smoking relapse in a 6-month follow-up after hospitalization for acute coronary syndrome

Objective The objective of the study was to investigate whether depression is a predictor of postdischarge smoking relapse among patients hospitalized for myocardial infarction (MI) or unstable angina (ILIA), in a smoke-free hospital. Methods Current smokers with MI or UA were interviewed while hospitalized; patients classified with major depression (MD) or no humor disorder were reinterviewed 6 months post discharge to ascertain smoking status. Potential predictors of relapse (depression; stress; anxiety; heart disease risk perception; coffee and alcohol consumption; sociodemographic, clinical, and smoking habit characteristics) were compared between those with MD (n = 268) and no humor disorder (n = 135). Results Relapsers (40.4%) were more frequently and more severely depressed, had higher anxiety and lower self-efficacy scale scores, diagnosis of UA, shorter hospitalizations, started smoking younger, made fewer attempts to quit, had a consort less often, and were more frequently at the `precontemplation` stage of change. Multivariate analysis showed relapse-positive predictors to be MD [odds ratio (OR): 2.549; 95% confidence interval (CI): 1.519-4.275] (P<0.001); `precontemplation` stage of change (OR: 7.798; 95% CI: 2.442-24.898) (P<0.001); previous coronary bypass graft surgery (OR: 4.062; 95% CI: 1.356-12.169) (P=0.012); and previous anxiolytic use (OR: 2.365; 95% CI: 1.095-5.107) (P=0.028). Negative predictors were diagnosis of MI (OR: 0.575; 95% CI: 0.361-0.916) (P=0.019); duration of hospitalization (OR: 0.935; 95% CI: 0.898-0.973) (P=0.001); smoking onset age (OR: 0.952; 95% CI: 0.910-0.994) (P=0.028); number of attempts to quit smoking (OR: 0.808; 95% CI: 0.678-0.964) (P=0.018); and `action` stage of change (OR: 0.065; 95% CI: 0.008-0.532) (P= 0.010). Conclusion Depression, no motivation, shorter hospitalization, and severity of illness contributed to postdischarge resumption of smoking by patients with acute coronary syndrome, who underwent hospital-initiated smoking cessation.

Distribution of HDL-cholesterol and non-HDL-cholesterol in Brazilian children and adolescents - The Floripa study

Background and aims: HDL-cholesterol (HDL-C) and non-HDL-cholesterol (nHDL-C) are involved in atherosclerosis. The aim of this study was to determine the distribution of HDL-C and nHDL-C and its association with cardiovascular and socio-cultural variables in a pediatric Brazilian sample. Methods and results: Children and adolescents from Florianopolis were randomly selected and a structured questionnaire was administered, a physical examination was performed and a blood sample was collected. Enzymatic and Direct methods in vitro were used to determine the total cholesterol and HDL-cholesterol levels. The associations among HDL-C and nHDL-C and the described variables were tested by odds ratio and logistic regression. A total of 1009 individuals were examined. Based on the Brazilian criteria, 23% were classified with low levels of HDL-C and 25% with high levels of non-HDL-C. After multivariate analysis there were significant associations among low HDL-C and high C-reactive protein (OR, 3.3; 95% CI, 2.1-5.2), paternal tobacco use (OR, 1.5; 95% CI, 1.1-2.1), and high triceps-to-subscapular index (OR, 1.5; 95% CI, 1.1-2.2). There were also significant associations among high nHDL-C and high waist circumference (OR, 1.95; 95% CI, 1.16-3.29), black skin color (OR, 1.78; 95% CI, 1.06-3.06), and high income (OR, 1.48; 95% CI, 1.09-2.02). Conclusions: In this sample, low levels of HDL-C were associated with other clinical variables such as a centripetal fat pattern and C-reactive protein, and n-HDL-C was associated with abdominal obesity, skin color and economic class. (C) 2009 Elsevier B. V. All rights reserved.

Anthropometric measures of increased central and overall adiposity in association with echocardiographic left ventricular hypertrophy

Left ventricular hypertrophy is an important predictor of cardiovascular risk and sudden death. This study explored the ability of four obesity indexes (body mass index, waist circumference, waist-hip ratio and waist-stature ratio) to identify left ventricular hypertrophy. A sample of the general population (n=682; 43.5% men) was surveyed to assess cardiovascular risk factors. Biochemical, anthropometric and blood pressure values were obtained in a clinic visit according to standard methods. Left ventricular mass was obtained from transthoracic echocardiogram. Left ventricular hypertrophy was defined using population-specific cutoff values for left ventricular mass indexed to height(2.7). The waist-stature ratio showed the strongest positive association with left ventricular mass. This correlation was stronger in women, even after controlling for age and systolic blood pressure. By multivariate analysis, the main predictors of left ventricular hypertrophy were waist-stature ratio (23%), systolic blood pressure (9%) and age (2%) in men, and waist-stature ratio (40%), age (6%) and systolic blood pressure (2%) in women. Receiver-operating characteristic curves showed the optimal cutoff values of the different anthropometric indexes associated with left ventricular hypertrophy. The waist-stature ratio was a significantly better predictor than the other indexes (except for the waist-hip ratio), independent of gender. It is noteworthy that a waist-stature ratio cutoff of 0.56 showed the highest combined sensitivity and specificity to detect left ventricular hypertrophy. Abdominal obesity identified by waist-stature ratio instead of overall obesity identified by body mass index is the simplest and best obesity index for assessing the risk of left ventricular hypertrophy, is a better predictor in women and has an optimal cutoff ratio of 0.56. Hypertension Research (2010) 33, 83-87; doi: 10.1038/hr.2009.188; published online 13 November 2009

A 1-year longitudinal study of severe traumatic brain injury in Australia using the Sickness Impact Profile

Objective: To document outcome and to investigate patterns of physical and psychosocial recovery in the first year following severe traumatic brain injury (TBI) in an Australian patient sample. Design: A longitudinal prospective study of a cohort of patients, with data collection at 3, 6, 9, and 12 months post injury. Setting: A head injury rehabilitation unit in a large metropolitan public hospital. Patients: A sample of 55 patients selected from 120 consecutive admissions with severe TBI. Patients who were more than 3 months post injury on admission, who remained confused, or who had severe communication deficits or a previous neurologic disorder were excluded. Interventions: All subjects participated in a multidisciplinary inpatient rehabilitation program, followed by varied participation in outpatient rehabilitation and community-based sen ices. Main Outcome Measures: The Sickness impact Profile (SIP) provided physical, psychosocial, and total dysfunction scores at each follow-up. Outcome at 1 year was measured by the Disability Rating Scale. Results: Multivariate analysis of variance indicated that the linear trend of recovery over time was less for psychosocial dysfunction than for physical dysfunction (F(1,51) = 5.87, P < .02). One rear post injury, 22% of subjects had returned to their previous level of employability, and 42% were able to live independently. Conclusions: Recovery from TBI in this Australian sample followed a pattern similar to that observed in other countries, with psychosocial dysfunction being more persistent. Self-report measures such as the SIP in TBI research are limited by problems of diminished self-awareness.

Reciprocal interactions of obstructive sleep apnea and hypertension associated with ACE I/D polymorphism in males

Background: The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism gene contributes to the genesis of hypertension (HTN) and may help explain the relationship between obstructive sleep apnea (OSA) and HTN. However, ACE is a pleiotropic gene that has several influences, including skeletal muscle and control of ventilation. We therefore tested the hypothesis that ACE polymorphism influences OSA severity. Methods: Male OSA patients (apnea-hypopnea index [AHI] > 5 events/h) from 2 university sleep centers were evaluated by polysomnography and ACE I/D polymorphism genotyping. Results: We studied 266 males with OSA (age = 48 +/- 13y, body mass index = 29 5kg/m(2), AHI = 34 +/- 25events/h). HTN was present in 114 patients (43%) who were older (p < 0.01), heavier (p < 0.05) and had more severe OSA (p < 0.01). The I allele was associated with HTN in patients with mild to moderate OSA (p < 0.01), but not in those with severe OSA. ACE I/D polymorphism was not associated with apnea severity among normotensive patients. In contrast. the only variables independently associated with OSA severity among patients with hypertension in multivariate analysis were BMI (OR = 1.12) and 11 genotype (OR = 0.27). Conclusions: Our results indicate reciprocal interactions between OSA and HTN with ACE I/D polymorphism, suggesting that among hypertensive OSA males, the homozygous ACE I allele protects from severe OSA. (C) 2009 Elsevier B.V. All rights reserved.